Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study.

Kulohoma, Benard W ORCID: 0000-0001-6825-1832, Marriage, Fiona, Vasieva, Olga, Mankhambo, Limangeni, Nguyen, Kha, Molyneux, Malcolm E, Molyneux, Elizabeth M, Day, Philip JR and Carrol, Enitan D
(2017) Peripheral blood RNA gene expression in children with pneumococcal meningitis: a prospective case-control study. BMJ paediatrics open, 1 (1). e000092 - ?.

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Introduction:Invasive pneumococcal disease (IPD), caused by Streptococcus pneumoniae, is a leading cause of pneumonia, meningitis and septicaemia worldwide, with increased morbidity and mortality in HIV-infected children. Objectives:We aimed to compare peripheral blood expression profiles between HIV-infected and uninfected children with pneumococcal meningitis and controls, and between survivors and non-survivors, in order to provide insight into the host inflammatory response leading to poorer outcomes. Design and setting:Prospective case-control observational study in a tertiary hospital in Malawi. Participants:Children aged 2 months to 16 years with pneumococcal meningitis or pneumonia. Methods:We used the human genome HGU133A Affymetrix array to explore differences in gene expression between cases with pneumococcal meningitis (n=12) and controls, and between HIV-infected and uninfected cases, and validated gene expression profiles for 34 genes using real-time quantitative PCR (RT-qPCR) in an independent set of cases with IPD (n=229) and controls (n=13). Pathway analysis was used to explore genes differentially expressed. Results:Irrespective of underlying HIV infection, cases showed significant upregulation compared with controls of the following: S100 calcium-binding protein A12 (S100A12); vanin-1 (VNN1); arginase, liver (ARG1); matrix metallopeptidase 9 (MMP9); annexin A3 (ANXA3); interleukin 1 receptor, type II (IL1R2); CD177 molecule (CD177); endocytic adaptor protein (NUMB) and S100 calcium-binding protein A9 (S100A9), cytoskeleton-associated protein 4 (CKAP4); and glycogenin 1 (GYG1). RT-qPCR confirmed differential expression in keeping with microarray results. There was no differential gene expression in HIV-infected compared with HIV-uninfected cases, but there was significant upregulation of folate receptor 3 (FOLR3), S100A12 in survivors compared with non-survivors. Conclusion:Children with IPD demonstrated increased expression in genes regulating immune activation, oxidative stress, leucocyte adhesion and migration, arginine metabolism, and glucocorticoid receptor signalling.

Item Type: Article
Depositing User: Symplectic Admin
Date Deposited: 07 Nov 2017 07:53
Last Modified: 09 Jan 2021 06:17
DOI: 10.1136/bmjpo-2017-000092